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4. Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.

Author

Conte, F., Sam, J.E., Lefeber, D.J., Passier, R., Conte, F., Sam, J.E., Lefeber, D.J., and Passier, R.

Abstract

Contains fulltext : 293293.pdf (Publisher’s version ) (Open Access), Heart failure (HF) is a progressive chronic disease that remains a primary cause of death worldwide, affecting over 64 million patients. HF can be caused by cardiomyopathies and congenital cardiac defects with monogenic etiology. The number of genes and monogenic disorders linked to development of cardiac defects is constantly growing and includes inherited metabolic disorders (IMDs). Several IMDs affecting various metabolic pathways have been reported presenting cardiomyopathies and cardiac defects. Considering the pivotal role of sugar metabolism in cardiac tissue, including energy production, nucleic acid synthesis and glycosylation, it is not surprising that an increasing number of IMDs linked to carbohydrate metabolism are described with cardiac manifestations. In this systematic review, we offer a comprehensive overview of IMDs linked to carbohydrate metabolism presenting that present with cardiomyopathies, arrhythmogenic disorders and/or structural cardiac defects. We identified 58 IMDs presenting with cardiac complications: 3 defects of sugar/sugar-linked transporters (GLUT3, GLUT10, THTR1); 2 disorders of the pentose phosphate pathway (G6PDH, TALDO); 9 diseases of glycogen metabolism (GAA, GBE1, GDE, GYG1, GYS1, LAMP2, RBCK1, PRKAG2, G6PT1); 29 congenital disorders of glycosylation (ALG3, ALG6, ALG9, ALG12, ATP6V1A, ATP6V1E1, B3GALTL, B3GAT3, COG1, COG7, DOLK, DPM3, FKRP, FKTN, GMPPB, MPDU1, NPL, PGM1, PIGA, PIGL, PIGN, PIGO, PIGT, PIGV, PMM2, POMT1, POMT2, SRD5A3, XYLT2); 15 carbohydrate-linked lysosomal storage diseases (CTSA, GBA1, GLA, GLB1, HEXB, IDUA, IDS, SGSH, NAGLU, HGSNAT, GNS, GALNS, ARSB, GUSB, ARSK). With this systematic review we aim to raise awareness about the cardiac presentations in carbohydrate-linked IMDs and draw attention to carbohydrate-linked pathogenic mechanisms that may underlie cardiac complications.

Published
2023

5. Mass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules

Author

van Loo, B., ten Den, S.A., Araújo-Gomes, N., de Jong, V., Snabel, R.R., Schot, M., Rivera-Arbeláez, J.M., Veenstra, G.J.C., Passier, R., Kamperman, T., Leijten, J., van Loo, B., ten Den, S.A., Araújo-Gomes, N., de Jong, V., Snabel, R.R., Schot, M., Rivera-Arbeláez, J.M., Veenstra, G.J.C., Passier, R., Kamperman, T., and Leijten, J.

Abstract

Item does not contain fulltext

Published
2023

7. Cardiomyocytes from Human Embryonic Stem Cells

Author

Passier, R., Denning, C., Mummery, C., Starke, K., editor, Born, G.V.R., editor, Eichelbaum, M., editor, Ganten, D., editor, Hofmann, F., editor, Rosenthal, W., editor, Rubanyi, G., editor, Wobus, Anna M., editor, and Boheler, Kenneth R., editor

Published
2006
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9. Conditional immortalization of human atrial myocytes for the generation of in vitro models of atrial fibrillation

Author

Harlaar, N., Dekker, S.O., Zhang, J., Snabel, R.R., Veldkamp, M.W., Verkerk, A.O., Fabres, C.C., Schwach, V., Lerink, L.J.S., Rivaud, M.R., Mulder, A.A., Corver, W.E., Goumans, M.J.T.H., Dobrev, D., Klautz, R.J.M., Schalij, M.J., Veenstra, G.J.C., Passier, R., Brakel, T.J. van, Pijnappels, D.A., Vries, A.A.F. de, Harlaar, N., Dekker, S.O., Zhang, J., Snabel, R.R., Veldkamp, M.W., Verkerk, A.O., Fabres, C.C., Schwach, V., Lerink, L.J.S., Rivaud, M.R., Mulder, A.A., Corver, W.E., Goumans, M.J.T.H., Dobrev, D., Klautz, R.J.M., Schalij, M.J., Veenstra, G.J.C., Passier, R., Brakel, T.J. van, Pijnappels, D.A., and Vries, A.A.F. de

Abstract

Contains fulltext : 251610.pdf (Publisher’s version ) (Closed access)

Published
2022

10. Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Author

Grapotte M., Saraswat M., Bessiere C., Menichelli C., Ramilowski J. A., Severin J., Hayashizaki Y., Itoh M., Tagami M., Murata M., Kojima-Ishiyama M., Noma S., Noguchi S., Kasukawa T., Hasegawa A., Suzuki H., Nishiyori-Sueki H., Frith M. C., Abugessaisa I., Aitken S., Aken B. L., Alam I., Alam T., Alasiri R., Alhendi A. M. N., Alinejad-Rokny H., Alvarez M. J., Andersson R., Arakawa T., Araki M., Arbel T., Archer J., Archibald A. L., Arner E., Arner P., Asai K., Ashoor H., Astrom G., Babina M., Baillie J. K., Bajic V. B., Bajpai A., Baker S., Baldarelli R. M., Balic A., Bansal M., Batagov A. O., Batzoglou S., Beckhouse A. G., Beltrami A. P., Beltrami C. A., Bertin N., Bhattacharya S., Bickel P. J., Blake J. A., Blanchette M., Bodega B., Bonetti A., Bono H., Bornholdt J., Bttcher M., Bougouffa S., Boyd M., Breda J., Brombacher F., Brown J. B., Bult C. J., Burroughs A. M., Burt D. W., Busch A., Caglio G., Califano A., Cameron C. J., Cannistraci C. V., Carbone A., Carlisle A. J., Carninci P., Carter K. W., Cesselli D., Chang J. -C., Chen J. C., Chen Y., Chierici M., Christodoulou J., Ciani Y., Clark E. L., Coskun M., Dalby M., Dalla E., Daub C. O., Davis C. A., de Hoon M. J. L., de Rie D., Denisenko E., Deplancke B., Detmar M., Deviatiiarov R., Di Bernardo D., Diehl A. D., Dieterich L. C., Dimont E., Djebali S., Dohi T., Dostie J., Drablos F., Edge A. S. B., Edinger M., Ehrlund A., Ekwall K., Elofsson A., Endoh M., Enomoto H., Enomoto S., Faghihi M., Fagiolini M., Farach-Carson M. C., Faulkner G. J., Favorov A., Fernandes A. M., Ferrai C., Forrest A. R. R., Forrester L. M., Forsberg M., Fort A., Francescatto M., Freeman T. C., Frith M., Fukuda S., Funayama M., Furlanello C., Furuno M., Furusawa C., Gao H., Gazova I., Gebhard C., Geier F., Geijtenbeek T. B. H., Ghosh S., Ghosheh Y., Gingeras T. R., Gojobori T., Goldberg T., Goldowitz D., Gough J., Greco D., Gruber A. J., Guhl S., Guigo R., Guler R., Gusev O., Gustincich S., Ha T. J., Haberle V., Hale P., Hallstrom B. M., Hamada M., Handoko L., Hara M., Harbers M., Harrow J., Harshbarger J., Hase T., Hashimoto K., Hatano T., Hattori N., Hayashi R., Herlyn M., Hettne K., Heutink P., Hide W., Hitchens K. J., Sui S. H., 't Hoen P. A. C., Hon C. C., Hori F., Horie M., Horimoto K., Horton P., Hou R., Huang E., Huang Y., Hugues R., Hume D., Ienasescu H., Iida K., Ikawa T., Ikemura T., Ikeo K., Inoue N., Ishizu Y., Ito Y., Ivshina A. V., Jankovic B. R., Jenjaroenpun P., Johnson R., Jorgensen M., Jorjani H., Joshi A., Jurman G., Kaczkowski B., Kai C., Kaida K., Kajiyama K., Kaliyaperumal R., Kaminuma E., Kanaya T., Kaneda H., Kapranov P., Kasianov A. S., Katayama T., Kato S., Kawaguchi S., Kawai J., Kawaji H., Kawamoto H., Kawamura Y. I., Kawasaki S., Kawashima T., Kempfle J. S., Kenna T. J., Kere J., Khachigian L., Kiryu H., Kishima M., Kitajima H., Kitamura T., Kitano H., Klaric E., Klepper K., Klinken S. P., Kloppmann E., Knox A. J., Kodama Y., Kogo Y., Kojima M., Kojima S., Komatsu N., Komiyama H., Kono T., Koseki H., Koyasu S., Kratz A., Kukalev A., Kulakovskiy I., Kundaje A., Kunikata H., Kuo R., Kuo T., Kuraku S., Kuznetsov V. A., Kwon T. J., Larouche M., Lassmann T., Law A., Le-Cao K. -A., Lecellier C. -H., Lee W., Lenhard B., Lennartsson A., Li K., Li R., Lilje B., Lipovich L., Lizio M., Lopez G., Magi S., Mak G. K., Makeev V., Manabe R., Mandai M., Mar J., Maruyama K., Maruyama T., Mason E., Mathelier A., Matsuda H., Medvedeva Y. A., Meehan T. F., Mejhert N., Meynert A., Mikami N., Minoda A., Miura H., Miyagi Y., Miyawaki A., Mizuno Y., Morikawa H., Morimoto M., Morioka M., Morishita S., Moro K., Motakis E., Motohashi H., Mukarram A. K., Mummery C. L., Mungall C. J., Murakawa Y., Muramatsu M., Nagasaka K., Nagase T., Nakachi Y., Nakahara F., Nakai K., Nakamura K., Nakamura Y., Nakazawa T., Nason G. P., Nepal C., Nguyen Q. H., Nielsen L. K., Nishida K., Nishiguchi K. M., Nishiyori H., Nitta K., Notredame C., Ogishima S., Ohkura N., Ohno H., Ohshima M., Ohtsu T., Okada Y., Okada-Hatakeyama M., Okazaki Y., Oksvold P., Orlando V., Ow G. S., Ozturk M., Pachkov M., Paparountas T., Parihar S. P., Park S. -J., Pascarella G., Passier R., Persson H., Philippens I. H., Piazza S., Plessy C., Pombo A., Ponten F., Poulain S., Poulsen T. M., Pradhan S., Prezioso C., Pridans C., Qin X. -Y., Quackenbush J., Rackham O., Ramilowski J., Ravasi T., Rehli M., Rennie S., Rito T., Rizzu P., Robert C., Roos M., Rost B., Roudnicky F., Roy R., Rye M. B., Sachenkova O., Saetrom P., Sai H., Saiki S., Saito M., Saito A., Sakaguchi S., Sakai M., Sakaue S., Sakaue-Sawano A., Sandelin A., Sano H., Sasamoto Y., Sato H., Saxena A., Saya H., Schafferhans A., Schmeier S., Schmidl C., Schmocker D., Schneider C., Schueler M., Schultes E. A., Schulze-Tanzil G., Semple C. A., Seno S., Seo W., Sese J., Sheng G., Shi J., Shimoni Y., Shin J. W., SimonSanchez J., Sivertsson A., Sjostedt E., Soderhall C., Laurent G. S., Stoiber M. H., Sugiyama D., Summers K. M., Suzuki A. M., Suzuki K., Suzuki M., Suzuki N., Suzuki T., Swanson D. J., Swoboda R. K., Taguchi A., Takahashi H., Takahashi M., Takamochi K., Takeda S., Takenaka Y., Tam K. T., Tanaka H., Tanaka R., Tanaka Y., Tang D., Taniuchi I., Tanzer A., Tarui H., Taylor M. S., Terada A., Terao Y., Testa A. C., Thomas M., Thongjuea S., Tomii K., Triglia E. T., Toyoda H., Tsang H. G., Tsujikawa M., Uhlen M., Valen E., van de Wetering M., van Nimwegen E., Velmeshev D., Verardo R., Vitezic M., Vitting-Seerup K., von Feilitzen K., Voolstra C. R., Vorontsov I. E., Wahlestedt C., Wasserman W. W., Watanabe K., Watanabe S., Wells C. A., Winteringham L. N., Wolvetang E., Yabukami H., Yagi K., Yamada T., Yamaguchi Y., Yamamoto M., Yamamoto Y., Yamanaka Y., Yano K., Yasuzawa K., Yatsuka Y., Yo M., Yokokura S., Yoneda M., Yoshida E., Yoshida Y., Yoshihara M., Young R., Young R. S., Yu N. Y., Yumoto N., Zabierowski S. E., Zhang P. G., Zucchelli S., Zwahlen M., Chatelain C., Brehelin L., Grapotte, M., Saraswat, M., Bessiere, C., Menichelli, C., Ramilowski, J. A., Severin, J., Hayashizaki, Y., Itoh, M., Tagami, M., Murata, M., Kojima-Ishiyama, M., Noma, S., Noguchi, S., Kasukawa, T., Hasegawa, A., Suzuki, H., Nishiyori-Sueki, H., Frith, M. C., Abugessaisa, I., Aitken, S., Aken, B. L., Alam, I., Alam, T., Alasiri, R., Alhendi, A. M. N., Alinejad-Rokny, H., Alvarez, M. J., Andersson, R., Arakawa, T., Araki, M., Arbel, T., Archer, J., Archibald, A. L., Arner, E., Arner, P., Asai, K., Ashoor, H., Astrom, G., Babina, M., Baillie, J. K., Bajic, V. B., Bajpai, A., Baker, S., Baldarelli, R. M., Balic, A., Bansal, M., Batagov, A. O., Batzoglou, S., Beckhouse, A. G., Beltrami, A. P., Beltrami, C. A., Bertin, N., Bhattacharya, S., Bickel, P. J., Blake, J. A., Blanchette, M., Bodega, B., Bonetti, A., Bono, H., Bornholdt, J., Bttcher, M., Bougouffa, S., Boyd, M., Breda, J., Brombacher, F., Brown, J. B., Bult, C. J., Burroughs, A. M., Burt, D. W., Busch, A., Caglio, G., Califano, A., Cameron, C. J., Cannistraci, C. V., Carbone, A., Carlisle, A. J., Carninci, P., Carter, K. W., Cesselli, D., Chang, J. -C., Chen, J. C., Chen, Y., Chierici, M., Christodoulou, J., Ciani, Y., Clark, E. L., Coskun, M., Dalby, M., Dalla, E., Daub, C. O., Davis, C. A., de Hoon, M. J. L., de Rie, D., Denisenko, E., Deplancke, B., Detmar, M., Deviatiiarov, R., Di Bernardo, D., Diehl, A. D., Dieterich, L. C., Dimont, E., Djebali, S., Dohi, T., Dostie, J., Drablos, F., Edge, A. S. B., Edinger, M., Ehrlund, A., Ekwall, K., Elofsson, A., Endoh, M., Enomoto, H., Enomoto, S., Faghihi, M., Fagiolini, M., Farach-Carson, M. C., Faulkner, G. J., Favorov, A., Fernandes, A. M., Ferrai, C., Forrest, A. R. R., Forrester, L. M., Forsberg, M., Fort, A., Francescatto, M., Freeman, T. C., Frith, M., Fukuda, S., Funayama, M., Furlanello, C., Furuno, M., Furusawa, C., Gao, H., Gazova, I., Gebhard, C., Geier, F., Geijtenbeek, T. B. H., Ghosh, S., Ghosheh, Y., Gingeras, T. R., Gojobori, T., Goldberg, T., Goldowitz, D., Gough, J., Greco, D., Gruber, A. J., Guhl, S., Guigo, R., Guler, R., Gusev, O., Gustincich, S., Ha, T. J., Haberle, V., Hale, P., Hallstrom, B. M., Hamada, M., Handoko, L., Hara, M., Harbers, M., Harrow, J., Harshbarger, J., Hase, T., Hashimoto, K., Hatano, T., Hattori, N., Hayashi, R., Herlyn, M., Hettne, K., Heutink, P., Hide, W., Hitchens, K. J., Sui, S. H., 't Hoen, P. A. C., Hon, C. C., Hori, F., Horie, M., Horimoto, K., Horton, P., Hou, R., Huang, E., Huang, Y., Hugues, R., Hume, D., Ienasescu, H., Iida, K., Ikawa, T., Ikemura, T., Ikeo, K., Inoue, N., Ishizu, Y., Ito, Y., Ivshina, A. V., Jankovic, B. R., Jenjaroenpun, P., Johnson, R., Jorgensen, M., Jorjani, H., Joshi, A., Jurman, G., Kaczkowski, B., Kai, C., Kaida, K., Kajiyama, K., Kaliyaperumal, R., Kaminuma, E., Kanaya, T., Kaneda, H., Kapranov, P., Kasianov, A. S., Katayama, T., Kato, S., Kawaguchi, S., Kawai, J., Kawaji, H., Kawamoto, H., Kawamura, Y. I., Kawasaki, S., Kawashima, T., Kempfle, J. S., Kenna, T. J., Kere, J., Khachigian, L., Kiryu, H., Kishima, M., Kitajima, H., Kitamura, T., Kitano, H., Klaric, E., Klepper, K., Klinken, S. P., Kloppmann, E., Knox, A. J., Kodama, Y., Kogo, Y., Kojima, M., Kojima, S., Komatsu, N., Komiyama, H., Kono, T., Koseki, H., Koyasu, S., Kratz, A., Kukalev, A., Kulakovskiy, I., Kundaje, A., Kunikata, H., Kuo, R., Kuo, T., Kuraku, S., Kuznetsov, V. A., Kwon, T. J., Larouche, M., Lassmann, T., Law, A., Le-Cao, K. -A., Lecellier, C. -H., Lee, W., Lenhard, B., Lennartsson, A., Li, K., Li, R., Lilje, B., Lipovich, L., Lizio, M., Lopez, G., Magi, S., Mak, G. K., Makeev, V., Manabe, R., Mandai, M., Mar, J., Maruyama, K., Maruyama, T., Mason, E., Mathelier, A., Matsuda, H., Medvedeva, Y. A., Meehan, T. F., Mejhert, N., Meynert, A., Mikami, N., Minoda, A., Miura, H., Miyagi, Y., Miyawaki, A., Mizuno, Y., Morikawa, H., Morimoto, M., Morioka, M., Morishita, S., Moro, K., Motakis, E., Motohashi, H., Mukarram, A. K., Mummery, C. L., Mungall, C. J., Murakawa, Y., Muramatsu, M., Nagasaka, K., Nagase, T., Nakachi, Y., Nakahara, F., Nakai, K., Nakamura, K., Nakamura, Y., Nakazawa, T., Nason, G. P., Nepal, C., Nguyen, Q. H., Nielsen, L. K., Nishida, K., Nishiguchi, K. M., Nishiyori, H., Nitta, K., Notredame, C., Ogishima, S., Ohkura, N., Ohno, H., Ohshima, M., Ohtsu, T., Okada, Y., Okada-Hatakeyama, M., Okazaki, Y., Oksvold, P., Orlando, V., Ow, G. S., Ozturk, M., Pachkov, M., Paparountas, T., Parihar, S. P., Park, S. -J., Pascarella, G., Passier, R., Persson, H., Philippens, I. H., Piazza, S., Plessy, C., Pombo, A., Ponten, F., Poulain, S., Poulsen, T. M., Pradhan, S., Prezioso, C., Pridans, C., Qin, X. -Y., Quackenbush, J., Rackham, O., Ramilowski, J., Ravasi, T., Rehli, M., Rennie, S., Rito, T., Rizzu, P., Robert, C., Roos, M., Rost, B., Roudnicky, F., Roy, R., Rye, M. B., Sachenkova, O., Saetrom, P., Sai, H., Saiki, S., Saito, M., Saito, A., Sakaguchi, S., Sakai, M., Sakaue, S., Sakaue-Sawano, A., Sandelin, A., Sano, H., Sasamoto, Y., Sato, H., Saxena, A., Saya, H., Schafferhans, A., Schmeier, S., Schmidl, C., Schmocker, D., Schneider, C., Schueler, M., Schultes, E. A., Schulze-Tanzil, G., Semple, C. A., Seno, S., Seo, W., Sese, J., Sheng, G., Shi, J., Shimoni, Y., Shin, J. W., Simonsanchez, J., Sivertsson, A., Sjostedt, E., Soderhall, C., Laurent, G. S., Stoiber, M. H., Sugiyama, D., Summers, K. M., Suzuki, A. M., Suzuki, K., Suzuki, M., Suzuki, N., Suzuki, T., Swanson, D. J., Swoboda, R. K., Taguchi, A., Takahashi, H., Takahashi, M., Takamochi, K., Takeda, S., Takenaka, Y., Tam, K. T., Tanaka, H., Tanaka, R., Tanaka, Y., Tang, D., Taniuchi, I., Tanzer, A., Tarui, H., Taylor, M. S., Terada, A., Terao, Y., Testa, A. C., Thomas, M., Thongjuea, S., Tomii, K., Triglia, E. T., Toyoda, H., Tsang, H. G., Tsujikawa, M., Uhlen, M., Valen, E., van de Wetering, M., van Nimwegen, E., Velmeshev, D., Verardo, R., Vitezic, M., Vitting-Seerup, K., von Feilitzen, K., Voolstra, C. R., Vorontsov, I. E., Wahlestedt, C., Wasserman, W. W., Watanabe, K., Watanabe, S., Wells, C. A., Winteringham, L. N., Wolvetang, E., Yabukami, H., Yagi, K., Yamada, T., Yamaguchi, Y., Yamamoto, M., Yamamoto, Y., Yamanaka, Y., Yano, K., Yasuzawa, K., Yatsuka, Y., Yo, M., Yokokura, S., Yoneda, M., Yoshida, E., Yoshida, Y., Yoshihara, M., Young, R., Young, R. S., Yu, N. Y., Yumoto, N., Zabierowski, S. E., Zhang, P. G., Zucchelli, S., Zwahlen, M., Chatelain, C., Brehelin, L., Institute of Biotechnology, Biosciences, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Computationnelle (IBC), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), National Institute of Advanced Industrial Science and Technology (AIST), SANOFI Recherche, University of British Columbia (UBC), Experimental Immunology, Infectious diseases, AII - Infectious diseases, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)

Subjects
0301 basic medicine, General Physics and Astronomy, Genome, Mice, 0302 clinical medicine, Transcription (biology), Promoter Regions, Genetic, Transcription Initiation, Genetic, 0303 health sciences, Multidisciplinary, 1184 Genetics, developmental biology, physiology, High-Throughput Nucleotide Sequencing, Neurodegenerative Diseases, 222 Other engineering and technologies, Genomics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], humanities, Enhancer Elements, Genetic, Microsatellite Repeat, Transcription Initiation Site, Sequence motif, Transcription Initiation, Human, Enhancer Elements, Neural Networks, Science, 610 Medicine & health, Computational biology, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Promoter Regions, 03 medical and health sciences, Computer, Deep Learning, Tandem repeat, Genetic, Clinical Research, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Machine learning, Genetics, Animals, Humans, Polymorphism, Enhancer, Transcriptomics, Gene, A549 Cell, 030304 developmental biology, Polymorphism, Genetic, Neurodegenerative Disease, Base Sequence, Animal, Genome, Human, Human Genome, Computational Biology, Promoter, General Chemistry, 113 Computer and information sciences, Cap analysis gene expression, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cardiovascular and Metabolic Diseases, A549 Cells, Minion, Generic health relevance, 3111 Biomedicine, Neural Networks, Computer, 610 Medizin und Gesundheit, 030217 neurology & neurosurgery, FANTOM consortium, Microsatellite Repeats
Abstract

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism., Nature Communications, 12 (1), ISSN:2041-1723

Published
2020

13. Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips

Author

Middelkamp, H.H.T., Verboven, A.H.A., Vivas, A.G. De Sá, Schoenmaker, C., Klein Gunnewiek, T.M., Passier, R., Albers, C.A., Hoen, P.A.C. 't, Nadif Kasri, N., Meer, A.D. van der, Middelkamp, H.H.T., Verboven, A.H.A., Vivas, A.G. De Sá, Schoenmaker, C., Klein Gunnewiek, T.M., Passier, R., Albers, C.A., Hoen, P.A.C. 't, Nadif Kasri, N., and Meer, A.D. van der

Abstract

Contains fulltext : 231651.pdf (publisher's version ) (Open Access), In vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with dedicated micro-compartments for neurons and vascular cells. Such multi-cell type organs-on-chips can emulate neurovascular unit (NVU) physiology, however there is a lack of systematic data on how individual cell types are affected by culturing on microfluidic systems versus conventional culture plates. This information can provide perspective on initial findings of studies using organs-on-chip models, and further optimizes these models in terms of cellular maturity and neurovascular physiology. Here, we analysed the transcriptomic profiles of co-cultures of human induced pluripotent stem cell (hiPSC)-derived neurons and rat astrocytes, as well as one-day monocultures of human endothelial cells, cultured on microfluidic chips. For each cell type, large gene expression changes were observed when cultured on microfluidic chips compared to conventional culture plates. Endothelial cells showed decreased cell division, neurons and astrocytes exhibited increased cell adhesion, and neurons showed increased maturity when cultured on a microfluidic chip. Our results demonstrate that culturing NVU cell types on microfluidic chips changes their gene expression profiles, presumably due to distinct surface-to-volume ratios and substrate materials. These findings inform further NVU organ-on-chip model optimization and support their future application in disease studies and drug testing.

Published
2021

14. ForceTracker: A versatile tool for contractile force assessment in 3D organ-on-chip platforms

Author

Rivera-Arbelaez, J.M. (author), Dostanic, M. (author), Stein, J.M. (author), van den Berg, A. (author), Segerink, L.I. (author), Mummery, C.L. (author), Sarro, Pasqualina M (author), Mastrangeli, Massimo (author), Ribeiro, M.C. (author), Passier, R. (author), Rivera-Arbelaez, J.M. (author), Dostanic, M. (author), Stein, J.M. (author), van den Berg, A. (author), Segerink, L.I. (author), Mummery, C.L. (author), Sarro, Pasqualina M (author), Mastrangeli, Massimo (author), Ribeiro, M.C. (author), and Passier, R. (author)

Abstract

Electronic Components, Technology and Materials

Published
2021

17. Musclemotion: A versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo

Author

Sala, L, Van Meer, B, Tertoolen, L, Bakkers, J, Bellin, M, Davis, R, Denning, C, Dieben, M, Eschenhagen, T, Giacomelli, E, Grandela, C, Hansen, A, Holman, E, Jongbloed, M, Kamel, S, Koopman, C, Lachaud, Q, Mannhardt, I, Mol, M, Mosqueira, D, Orlova, V, Passier, R, Ribeiro, M, Saleem, U, Smith, G, Burton, F, Mummery, C, Sala L., Van Meer B. J., Tertoolen L. G. J., Bakkers J., Bellin M., Davis R. P., Denning C., Dieben M. A. E., Eschenhagen T., Giacomelli E., Grandela C., Hansen A., Holman E. R., Jongbloed M. R. M., Kamel S. M., Koopman C. D., Lachaud Q., Mannhardt I., Mol M. P. H., Mosqueira D., Orlova V. V., Passier R., Ribeiro M. C., Saleem U., Smith G. L., Burton F. L., Mummery C. L., Sala, L, Van Meer, B, Tertoolen, L, Bakkers, J, Bellin, M, Davis, R, Denning, C, Dieben, M, Eschenhagen, T, Giacomelli, E, Grandela, C, Hansen, A, Holman, E, Jongbloed, M, Kamel, S, Koopman, C, Lachaud, Q, Mannhardt, I, Mol, M, Mosqueira, D, Orlova, V, Passier, R, Ribeiro, M, Saleem, U, Smith, G, Burton, F, Mummery, C, Sala L., Van Meer B. J., Tertoolen L. G. J., Bakkers J., Bellin M., Davis R. P., Denning C., Dieben M. A. E., Eschenhagen T., Giacomelli E., Grandela C., Hansen A., Holman E. R., Jongbloed M. R. M., Kamel S. M., Koopman C. D., Lachaud Q., Mannhardt I., Mol M. P. H., Mosqueira D., Orlova V. V., Passier R., Ribeiro M. C., Saleem U., Smith G. L., Burton F. L., and Mummery C. L.

Abstract

Rationale: There are several methods to measure cardiomyocyte and muscle contraction, but these require customized hardware, expensive apparatus, and advanced informatics or can only be used in single experimental models. Consequently, data and techniques have been difficult to reproduce across models and laboratories, analysis is time consuming, and only specialist researchers can quantify data. Objective: Here, we describe and validate an automated, open-source software tool (MUSCLEMOTION) adaptable for use with standard laboratory and clinical imaging equipment that enables quantitative analysis of normal cardiac contraction, disease phenotypes, and pharmacological responses. Methods and Results: MUSCLEMOTION allowed rapid and easy measurement of movement from high-speed movies in (1) 1-dimensional in vitro models, such as isolated adult and human pluripotent stem cell-derived cardiomyocytes; (2) 2-dimensional in vitro models, such as beating cardiomyocyte monolayers or small clusters of human pluripotent stem cell-derived cardiomyocytes; (3) 3-dimensional multicellular in vitro or in vivo contractile tissues, such as cardiac “organoids,” engineered heart tissues, and zebrafish and human hearts. MUSCLEMOTION was effective under different recording conditions (bright-field microscopy with simultaneous patch-clamp recording, phase contrast microscopy, and traction force microscopy). Outcomes were virtually identical to the current gold standards for contraction measurement, such as optical flow, post deflection, edge-detection systems, or manual analyses. Finally, we used the algorithm to quantify contraction in in vitro and in vivo arrhythmia models and to measure pharmacological responses. Conclusions: Using a single open-source method for processing video recordings, we obtained reliable pharmacological data and measures of cardiac disease phenotype in experimental cell, animal, and human models.

Published
2018

22. Standardized, modular microfluidic building blocks for automated cell culturing systems

Author

Vollertsen, A., Bossink, E., Dean de Boer, Spalink, J., Passier, R., Den Berg, A., Segerink, L., Meer, A., Odijk, M., Biomedical and Environmental Sensorsystems, and Applied Stem Cell Technology

Subjects
Automation, Modular, Chemical Engineering (miscellaneous), Bioengineering, Microfluidic Building Blocks, Standardization
Abstract

We report an emerging toolkit of modular and standardized MicroFluidic Building Blocks (MFBB) to ultimately form a versatile and automated system on a Fluidic Circuit Board (FCB) for high-throughput cell culturing and screening assays. The toolkit is composed of four different MFBBs to meet a total of four different purposes: (1) a metering and mixing MFBB for upstream sample preparation, (2) a gut-on-a-chip MFBB for increased biological complexity, (3) a 64-chamber MFBB for multiplexed cell culturing, and (4) a cell-in-droplet encapsulation MFBB for downstream analysis preparation.

Published
2019

23. Microfabricated tuneable and transferable porous PDMS membranes for Organs-on-Chips

Author

Quiros Solano, W.F. (author), Gaio, N. (author), Stassen, O.M.J.A. (author), Arik, Y.B. (author), Silvestri, C. (author), Van Engeland, N.C.A. (author), Van der Meer, A. (author), Passier, R. (author), Sahlgren, C.M. (author), Bouten, C.V.C. (author), van den Berg, A. (author), Dekker, R. (author), Sarro, Pasqualina M (author), Quiros Solano, W.F. (author), Gaio, N. (author), Stassen, O.M.J.A. (author), Arik, Y.B. (author), Silvestri, C. (author), Van Engeland, N.C.A. (author), Van der Meer, A. (author), Passier, R. (author), Sahlgren, C.M. (author), Bouten, C.V.C. (author), van den Berg, A. (author), Dekker, R. (author), and Sarro, Pasqualina M (author)

Abstract

We present a novel and highly reproducible process to fabricate transferable porous PDMS membranes for PDMS-based Organs-on-Chips (OOCs) using microelectromechanical systems (MEMS) fabrication technologies. Porous PDMS membranes with pore sizes down to 2.0 μm in diameter and a wide porosity range (2–65%) can be fabricated. To overcome issues normally faced when using replica moulding and extend the applicability to most OOCs and improve their scalability and reproducibility, the process includes a sacrificial layer to easily transfer the membranes from a silicon carrier to any PDMS-based OOC. The highly reliable fabrication and transfer method does not need of manual handling to define the pore features (size, distribution), allowing very thin (<10 μm) functional membranes to be transferred at chip level with a high success rate (85%). The viability of cell culturing on the porous membranes was assessed by culturing two different cell types on transferred membranes in two different OOCs. Human umbilical endothelial cells (HUVEC) and MDA-MB-231 (MDA) cells were successfully cultured confirming the viability of cell culturing and the biocompatibility of the membranes. The results demonstrate the potential of controlling the porous membrane features to study cell mechanisms such as transmigrations, monolayer formation, and barrier function. The high control over the membrane characteristics might consequently allow to intentionally trigger or prevent certain cellular responses or mechanisms when studying human physiology and pathology using OOCs., Electronic Components, Technology and Materials

Published
2018
Full Text
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24. Microfabricated tuneable and transferable porous PDMS membranes for Organs-on-Chips

Author

Quirós-Solano, W.F., Gaio, N., Stassen, O.M.J.A., Arik, Y.B., Silvestri, C, van Engeland, N.C.A., van der Meer, A., Passier, R., Sahlgren, C.M., Bouten, C.V.C., van den Berg, A., Dekker, R., Sarro, P.M., Quirós-Solano, W.F., Gaio, N., Stassen, O.M.J.A., Arik, Y.B., Silvestri, C, van Engeland, N.C.A., van der Meer, A., Passier, R., Sahlgren, C.M., Bouten, C.V.C., van den Berg, A., Dekker, R., and Sarro, P.M.

Abstract

We present a novel and highly reproducible process to fabricate transferable porous PDMS membranes for PDMS-based Organs-on-Chips (OOCs) using microelectromechanical systems (MEMS) fabrication technologies. Porous PDMS membranes with pore sizes down to 2.0 μm in diameter and a wide porosity range (2-65%) can be fabricated. To overcome issues normally faced when using replica moulding and extend the applicability to most OOCs and improve their scalability and reproducibility, the process includes a sacrificial layer to easily transfer the membranes from a silicon carrier to any PDMS-based OOC. The highly reliable fabrication and transfer method does not need of manual handling to define the pore features (size, distribution), allowing very thin (<10 μm) functional membranes to be transferred at chip level with a high success rate (85%). The viability of cell culturing on the porous membranes was assessed by culturing two different cell types on transferred membranes in two different OOCs. Human umbilical endothelial cells (HUVEC) and MDA-MB-231 (MDA) cells were successfully cultured confirming the viability of cell culturing and the biocompatibility of the membranes. The results demonstrate the potential of controlling the porous membrane features to study cell mechanisms such as transmigrations, monolayer formation, and barrier function. The high control over the membrane characteristics might consequently allow to intentionally trigger or prevent certain cellular responses or mechanisms when studying human physiology and pathology using OOCs.

Published
2018

25. NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network

Author

Anderson, DJ, Kaplan, DI, Bell, KM, Koutsis, K, Haynes, JM, Mills, RJ, Phelan, DG, Qian, EL, Leitoguinho, AR, Arasaratnam, D, Labonne, T, Ng, ES, Davis, RP, Casini, S, Passier, R, Hudson, JE, Porrello, ER, Costa, MW, Rafii, A, Curl, CL, Delbridge, LM, Harvey, RP, Oshlack, A, Cheung, MM, Mummery, CL, Petrou, S, Elefanty, AG, Stanley, EG, Elliott, DA, Anderson, DJ, Kaplan, DI, Bell, KM, Koutsis, K, Haynes, JM, Mills, RJ, Phelan, DG, Qian, EL, Leitoguinho, AR, Arasaratnam, D, Labonne, T, Ng, ES, Davis, RP, Casini, S, Passier, R, Hudson, JE, Porrello, ER, Costa, MW, Rafii, A, Curl, CL, Delbridge, LM, Harvey, RP, Oshlack, A, Cheung, MM, Mummery, CL, Petrou, S, Elefanty, AG, Stanley, EG, and Elliott, DA

Abstract

Congenital heart defects can be caused by mutations in genes that guide cardiac lineage formation. Here, we show deletion of NKX2-5, a critical component of the cardiac gene regulatory network, in human embryonic stem cells (hESCs), results in impaired cardiomyogenesis, failure to activate VCAM1 and to downregulate the progenitor marker PDGFRα. Furthermore, NKX2-5 null cardiomyocytes have abnormal physiology, with asynchronous contractions and altered action potentials. Molecular profiling and genetic rescue experiments demonstrate that the bHLH protein HEY2 is a key mediator of NKX2-5 function during human cardiomyogenesis. These findings identify HEY2 as a novel component of the NKX2-5 cardiac transcriptional network, providing tangible evidence that hESC models can decipher the complex pathways that regulate early stage human heart development. These data provide a human context for the evaluation of pathogenic mutations in congenital heart disease.

Published
2018

28. Data Descriptor: FANTOM5 CAGE profiles of human and mouse samples

Author

Noguchi, S, Arakawa, T, Fukuda, S, Furuno, M, Hasegawa, A, Hori, F, Ishikawa-Kato, S, Kaida, K, Kaiho, A, Kanamori-Katayama, M, Kawashima, T, Kojima, M, Kubosaki, A, Manabe, R-I, Murata, M, Nagao-Sato, S, Nakazato, K, Ninomiya, N, Nishiyori-Sueki, H, Noma, S, Saijyo, E, Saka, A, Sakai, M, Simon, C, Suzuki, N, Tagami, M, Watanabe, S, Yoshida, S, Arner, P, Axton, RA, Babina, M, Baillie, JK, Barnett, TC, Beckhouse, AG, Blumenthal, A, Bodega, B, Bonetti, A, Briggs, J, Brombacher, F, Carlisle, AJ, Clevers, HC, Davis, CA, Detmar, M, Dohi, T, Edge, ASB, Edinger, M, Ehrlund, A, Ekwall, K, Endoh, M, Enomoto, H, Eslami, A, Fagiolini, M, Fairbairn, L, Farach-Carson, MC, Faulkner, GJ, Ferrai, C, Fisher, ME, Forrester, LM, Fujita, R, Furusawa, J-I, Geijtenbeek, TB, Gingeras, T, Goldowitz, D, Guhl, S, Guler, R, Gustincich, S, Ha, TJ, Hamaguchi, M, Hara, M, Hasegawa, Y, Herlyn, M, Heutink, P, Hitchens, KJ, Hume, DA, Ikawa, T, Ishizu, Y, Kai, C, Kawamoto, H, Kawamura, YI, Kempfle, JS, Kenna, TJ, Kere, J, Khachigian, LM, Kitamura, T, Klein, S, Klinken, SP, Knox, AJ, Kojima, S, Koseki, H, Koyasu, S, Lee, W, Lennartsson, A, Mackay-sim, A, Mejhert, N, Mizuno, Y, Morikawa, H, Morimoto, M, Moro, K, Morris, KJ, Motohashi, H, Mummery, CL, Nakachi, Y, Nakahara, F, Nakamura, T, Nakamura, Y, Nozaki, T, Ogishima, S, Ohkura, N, Ohno, H, Ohshima, M, Okada-Hatakeyama, M, Okazaki, Y, Orlando, V, Ovchinnikov, DA, Passier, R, Patrikakis, M, Pombo, A, Pradhan-Bhatt, S, Qin, X-Y, Rehli, M, Rizzu, P, Roy, S, Sajantila, A, Sakaguchi, S, Sato, H, Satoh, H, Savvi, S, Saxena, A, Schmidl, C, Schneider, C, Schulze-Tanzil, GG, Schwegmann, A, Sheng, G, Shin, JW, Sugiyama, D, Sugiyama, T, Summers, KM, Takahashi, N, Takai, J, Tanaka, H, Tatsukawa, H, Tomoiu, A, Toyoda, H, van de Wetering, M, van den Berg, LM, Verardo, R, Vijayan, D, Wells, CA, Winteringham, LN, Wolvetang, E, Yamaguchi, Y, Yamamoto, M, Yanagi-Mizuochi, C, Yoneda, M, Yonekura, Y, Zhang, PG, Zucchelli, S, Abugessaisa, I, Arner, E, Harshbarger, J, Kondo, A, Lassmann, T, Lizio, M, Sahin, S, Sengstag, T, Severin, J, Shimoji, H, Suzuki, M, Suzuki, H, Kawai, J, Kondo, N, Itoh, M, Daub, CO, Kasukawa, T, Kawaji, H, Carninci, P, Forrest, ARR, Hayashizaki, Y, Noguchi, S, Arakawa, T, Fukuda, S, Furuno, M, Hasegawa, A, Hori, F, Ishikawa-Kato, S, Kaida, K, Kaiho, A, Kanamori-Katayama, M, Kawashima, T, Kojima, M, Kubosaki, A, Manabe, R-I, Murata, M, Nagao-Sato, S, Nakazato, K, Ninomiya, N, Nishiyori-Sueki, H, Noma, S, Saijyo, E, Saka, A, Sakai, M, Simon, C, Suzuki, N, Tagami, M, Watanabe, S, Yoshida, S, Arner, P, Axton, RA, Babina, M, Baillie, JK, Barnett, TC, Beckhouse, AG, Blumenthal, A, Bodega, B, Bonetti, A, Briggs, J, Brombacher, F, Carlisle, AJ, Clevers, HC, Davis, CA, Detmar, M, Dohi, T, Edge, ASB, Edinger, M, Ehrlund, A, Ekwall, K, Endoh, M, Enomoto, H, Eslami, A, Fagiolini, M, Fairbairn, L, Farach-Carson, MC, Faulkner, GJ, Ferrai, C, Fisher, ME, Forrester, LM, Fujita, R, Furusawa, J-I, Geijtenbeek, TB, Gingeras, T, Goldowitz, D, Guhl, S, Guler, R, Gustincich, S, Ha, TJ, Hamaguchi, M, Hara, M, Hasegawa, Y, Herlyn, M, Heutink, P, Hitchens, KJ, Hume, DA, Ikawa, T, Ishizu, Y, Kai, C, Kawamoto, H, Kawamura, YI, Kempfle, JS, Kenna, TJ, Kere, J, Khachigian, LM, Kitamura, T, Klein, S, Klinken, SP, Knox, AJ, Kojima, S, Koseki, H, Koyasu, S, Lee, W, Lennartsson, A, Mackay-sim, A, Mejhert, N, Mizuno, Y, Morikawa, H, Morimoto, M, Moro, K, Morris, KJ, Motohashi, H, Mummery, CL, Nakachi, Y, Nakahara, F, Nakamura, T, Nakamura, Y, Nozaki, T, Ogishima, S, Ohkura, N, Ohno, H, Ohshima, M, Okada-Hatakeyama, M, Okazaki, Y, Orlando, V, Ovchinnikov, DA, Passier, R, Patrikakis, M, Pombo, A, Pradhan-Bhatt, S, Qin, X-Y, Rehli, M, Rizzu, P, Roy, S, Sajantila, A, Sakaguchi, S, Sato, H, Satoh, H, Savvi, S, Saxena, A, Schmidl, C, Schneider, C, Schulze-Tanzil, GG, Schwegmann, A, Sheng, G, Shin, JW, Sugiyama, D, Sugiyama, T, Summers, KM, Takahashi, N, Takai, J, Tanaka, H, Tatsukawa, H, Tomoiu, A, Toyoda, H, van de Wetering, M, van den Berg, LM, Verardo, R, Vijayan, D, Wells, CA, Winteringham, LN, Wolvetang, E, Yamaguchi, Y, Yamamoto, M, Yanagi-Mizuochi, C, Yoneda, M, Yonekura, Y, Zhang, PG, Zucchelli, S, Abugessaisa, I, Arner, E, Harshbarger, J, Kondo, A, Lassmann, T, Lizio, M, Sahin, S, Sengstag, T, Severin, J, Shimoji, H, Suzuki, M, Suzuki, H, Kawai, J, Kondo, N, Itoh, M, Daub, CO, Kasukawa, T, Kawaji, H, Carninci, P, Forrest, ARR, and Hayashizaki, Y

Abstract

In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.

Published
2017

30. Versatile open software to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo

Author

Sala, L., primary, van Meer, B.J., additional, Tertoolen, L.G.J., additional, Bakkers, J., additional, Bellin, M., additional, Davis, R.P., additional, Denning, C., additional, Dieben, M.A.E., additional, Eschenhagen, T., additional, Giacomelli, E., additional, Grandela, C., additional, Hansen, A., additional, Holman, E.R., additional, Jongbloed, M.R. M., additional, Kamel, S.M., additional, Koopman, C.D., additional, Lachaud, Q., additional, Mannhardt, I., additional, Mol, M.P.H., additional, Orlova, V.V., additional, Passier, R., additional, Ribeiro, M.C., additional, Saleem, U., additional, Smith, G.L., additional, Mummery, C.L., additional, and Burton, F.L., additional

Published
2017
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33. The statistical geometry of transcriptome divergence in cell-type evolution and cancer

Author

Liang, C, Alam, I, Albanese, D, Altschuler, G, Andersson, R, Arakawa, T, Archer, J, Arner, E, Arner, P, Babina, M, Baillie, K, Bajic, V, Baker, S, Balic, A, Balwierz, P, Beckhouse, A, Bertin, N, Blake, Ja, Blumenthal, A, Bodega, B, Bonetti, A, Briggs, J, Brombacher, F, Burroughs, M, Califano, A, Cannistraci, C, Carbajo, D, Carninci, P, Chen, Yang, Chierici, M, Ciani, Y, Clevers, H, Dalla, Emiliano, Daub, C, Davis, C, De Hoon, M, De Lima Morais, D, Dermar, M, Diehl, A, Dimont, E, Dohl, T, Drabros, F, Edge, A, Edinger, M, Ekwall, K, Endoh, M, Enomoto, H, Fagiolini, M, Fairbairn, L, Fang, H, Farach Carson, Mc, Faulkner, G, Favorov, A, Fisher, M, Forrest, A, Francescatto, M, Freeman, T, Frith, M, Fujita, R, Fukuda, S, Furlanello, C, Furuno, M, Furusawa, J, Geijtenbeek, Tb, Gibson, A, Gingeras, T, Goldowithz, D, Gough, J, Guhl, S, Guler, R, Gustincich, Stefano, Ha, T, Haberle, V, Hamaguchi, M, Hara, M, Harbers, M, Harshbarger, J, Hasegawa, A, Hasegawa, Y, Hashimoto, T, Hayashizaki, Y, Herlyn, M, Heutink, P, Hide, W, Hitchens, K, Ho Sui, S, Hofmann, O, Hoof, I, Hori, F, Hume, D, Huminiecki, L, Iida, K, Ikawa, T, Ishizu, Y, Itoh, M, Jankovic, B, Jia, H, Jorgensen, M, Joshi, A, Jurman, G, Kaczkowski, B, Kai, C, Kaida, K, Kaiho, A, Kajiyama, K, Kanamori Katayama, M, Kasianov, A, Kasukawa, T, Katayama, S, Kato Ishikawa, S, Kawaguchi, S, Kawai, J, Kawaji, H, Kawamoto, H, Kawamura, Y, Kawashima, T, Kempfle, J, Kenna, T, Kere, J, Khachigian, L, Kitamura, T, Klinken, P, Knox, A, Kojima, M, Kojima, S, Kondo, N, Koseki, H, Koyasu, S, Krampitz, S, Kubosaki, A, Kulakovskiy, I, Kwon, At, Laros, J, Lassmann, T, Lenhard, B, Lennartsson, A, Li, K, Lilji, B, Lipovich, L, Lizio, M, Mackay Sim, A, Makeev, V, Manabe, R, Mar, J, Marchand, B, Mathelier, A, Medvedeva, Y, Meehan, Tf, Mejhert, N, Meynert, A, Mizuno, Y, Morikawa, H, Morimoto, M, Moro, K, Motakis, E, Motohashi, H, Mummery, C, Mungall, Cj, Murata, M, Nagao Sato, S, Nakachi, Y, Nakahara, F, Nakamura, T, Nakamura, Y, Nakazato, K, Ninomiya Fukuda, N, Nishiyori Sueki, H, Noma, S, Nozaki, T, Ogishima, S, Ohkura, N, Ohmiya, H, Ohno, H, Ohshima, M, Okada Hatakeyama, M, Okazaki, Y, Orlando, V, Ovchinnikov, D, Pain, A, Passier, R, Persson, H, Piazza, Silvano, Plessy, C, Pradhan Bhatt, S, Prendergast, J, Rackham, O, Ramilowski, J, Rashid, M, Ravasi, T, Rehli, M, Rizzu, P, Roncador, M, Roy, S, Rye, M, Saijyo, E, Sajantila, A, Saka, A, Sakaguchi, S, Sakai, M, Sandelin, A, Sato, H, Satoh, H, Suzana, S, Alka, S, Schaefer, U, Schmeier, S, Schmidl, C, Schneider, C, Schultes, Ea, Schulze Tanzil, G, Schwegmann, A, Semple, C, Sengstag, T, Severin, J, Sheng, G, Shimoji, H, Shimoni, Y, Shin, J, Simon, C, Sugiyama, D, Sugiyama, T, Summers, K, Suzuki, H, Suzuki, M, Suzuki, N, Swoboda, R, Hoen P, T, Tagami, M, Takahashi, N, Takai, J, Tanaka, H, Tatsukawa, H, Tatum, Z, Taylor, M, Thompson, M, Toyoda, H, Toyoda, T, Valen, E, Van De Wetering, M, Van Den Berg, L, Van Nimwegen, E, Verardo, R, Vijayan, D, Vitezic, M, Vorontzov, I, Wasserman, W, Watanabe, S, Wells, C, Winteringham, L, Wolvetang, E, Wood, Ej, Yamaguchi, Y, Yamamoto, M, Yoneda, M, Yonekura, Y, Yoshida, Shin'Ichirou, Young, R, Zabierowski, Se, Zhang, P, Zhao, X, Zucchelli, Silvia, Forrest, Ar, Wagner, Gp, Hubrecht Institute for Developmental Biology and Stem Cell Research, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, and Experimental Immunology

Subjects
Cell type, General Physics and Astronomy, rna-seq data, phylogenetic networks, Biology, ENCODE, General Biochemistry, Genetics and Molecular Biology, Divergence, Transcriptome, Models, Settore BIO/13 - Biologia Applicata, Neoplasms, Humans, Genetics, Models, Statistical, Multidisciplinary, Statistical model, General Chemistry, Statistical, Biological Evolution, Body plan, Tree structure, Evolutionary biology, Cancer cell
Abstract

In evolution, body plan complexity increases due to an increase in the number of individualized cell types. Yet, there is very little understanding of the mechanisms that produce this form of organismal complexity. One model for the origin of novel cell types is the sister cell-type model. According to this model, each cell type arises together with a sister cell type through specialization from an ancestral cell type. A key prediction of the sister cell-type model is that gene expression profiles of cell types exhibit tree structure. Here we present a statistical model for detecting tree structure in transcriptomic data and apply it to transcriptomes from ENCODE and FANTOM5. We show that transcriptomes of normal cells harbour substantial amounts of hierarchical structure. In contrast, cancer cell lines have less tree structure, suggesting that the emergence of cancer cells follows different principles from that of evolutionary cell-type origination.

Published
2015

34. Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation

Author

Morikawa, H, Ohkura, N, Vandenbon, A, Itoh, M, Nagao Sato, S, Kawaji, H, Lassmann, T, Carninci, P, Hayashizaki, Y, Forrest, Ar, Standley, Dm, Date, H, Sakaguchi, S, FANTOM Consortium (Forrest AR, Rehli, M, Baillie, Jk, de Hoon MJ, Haberle, V, Kulakovskiy, Iv, Lizio, M, Andersson, R, Mungall, Cj, Meehan, Tf, Schmeier, S, Bertin, N, Jørgensen, M, Dimont, E, Arner, E, Schmidl, C, Schaefer, U, Medvedeva, Ya, Plessy, C, Vitezic, M, Severin, J, Semple, Ca, Ishizu, Y, Francescatto, M, Alam, I, Albanese, D, Altschuler, Gm, Archer, Ja, Arner, P, Babina, M, Baker, S, Balwierz, Pj, Beckhouse, Ag, Pradhan Bhatt, S, Blake, Ja, Blumenthal, A, Bodega, B, Bonetti, A, Briggs, J, Brombacher, F, Burroughs, Am, Califano, A, Cannistraci, Cv, Carbajo, D, Chen, Y, Chierici, M, Ciani, Y, Clevers, Hc, Dalla, E, Davis, Ca, Deplancke, B, Detmar, M, Diehl, Ad, Dohi, T, Drabløs, F, Edge, As, Edinger, M, Ekwall, K, Endoh, M, Enomoto, H, Fagiolini, M, Fairbairn, L, Fang, H, Farach Carson MC, Faulkner, Gj, Favorov, Av, Fisher, Me, Frith, Mc, Fujita, R, Fukuda, S, Furlanello, C, Furuno, M, Furusawa, J, Geijtenbeek, Tb, Gibson, A, Gingeras, T, Goldowitz, D, Gough, J, Guhl, S, Guler, R, Gustincich, Stefano, Ha, Tj, Hamaguchi, M, Hara, M, Harbers, M, Harshbarger, J, Hasegawa, A, Hasegawa, Y, Hashimoto, T, Herlyn, M, Hitchens, Kj, Ho Sui SJ, Hofmann, Om, Hoof, I, Hori, F, Huminiecki, L, Iida, K, Ikawa, T, Jankovic, Br, Jia, H, Joshi, A, Jurman, G, Kaczkowski, B, Kai, C, Kaida, K, Kaiho, A, Kajiyama, K, Kanamori Katayama, M, Kasianov, As, Kasukawa, T, Katayama, S, Kato, S, Kawaguchi, S, Kawamoto, H, Kawamura, Yi, Kawashima, T, Kempfle, Js, Kenna, Tj, Kere, J, Khachigian, Lm, Kitamura, T, Klinken, Sp, Knox, Aj, Kojima, M, Kojima, S, Kondo, N, Koseki, H, Koyasu, S, Krampitz, S, Kubosaki, A, Kwon, At, Laros, Jf, Lee, W, Lennartsson, A, Li, K, Lilje, B, Lipovich, L, Mackay Sim, A, Manabe, R, Mar, Jc, Marchand, B, Mathelier, A, Mejhert, N, Meynert, A, Mizuno, Y, Morais, Da, Morimoto, M, Moro, K, Motakis, E, Motohashi, H, Mummery, Cl, Murata, M, Nakachi, Y, Nakahara, F, Nakamura, T, Nakamura, Y, Nakazato, K, van Nimwegen, E, Ninomiya, N, Nishiyori, H, Noma, S, Nozaki, T, Ogishima, S, Ohmiya, H, Ohno, H, Ohshima, M, Okada Hatakeyama, M, Okazaki, Y, Orlando, V, Ovchinnikov, Da, Pain, A, Passier, R, Patrikakis, M, Persson, H, Piazza, S, Prendergast, Jg, Rackham, Oj, Ramilowski, Ja, Rashid, M, Ravasi, T, Rizzu, P, Roncador, M, Roy, S, Rye, Mb, Saijyo, E, Sajantila, A, Saka, A, Sakai, M, Sato, H, Satoh, H, Savvi, S, Saxena, A, Schneider, C, Schultes, Ea, Schulze Tanzil GG, Schwegmann, A, Sengstag, T, Sheng, G, Shimoji, H, Shimoni, Y, Shin, Jw, Simon, C, Sugiyama, D, Sugiyama, T, Suzuki, M, Swoboda, Rk, 't Hoen PA, Tagami, M, Takahashi, N, Takai, J, Tanaka, H, Tatsukawa, H, Tatum, Z, Thompson, M, Toyoda, H, Toyoda, T, Valen, E, van de Wetering, M, van den Berg LM, Verardo, R, Vijayan, D, Vorontsov, Ie, Wasserman, Ww, Watanabe, S, Wells, Ca, Winteringham, Ln, Wolvetang, E, Wood, Ej, Yamaguchi, Y, Yamamoto, M, Yoneda, M, Yonekura, Y, Yoshida, S, Zabierowski, Se, Zhang, Pg, Zhao, X, Zucchelli, S, Summers, Km, Suzuki, H, Daub, Co, Kawai, J, Heutink, P, Hide, W, Freeman, Tc, Lenhard, B, Bajic, Vb, Taylor, Ms, Makeev, Vj, Sandelin, A, Hume, Da, Hayashizaki, Y., AII - Amsterdam institute for Infection and Immunity, Infectious diseases, Experimental Immunology, and Hubrecht Institute for Developmental Biology and Stem Cell Research

Subjects
Transcription, Genetic, Regulatory T cell, T-Lymphocytes, Down-Regulation, chemical and pharmacologic phenomena, Biology, Inbred C57BL, T-Lymphocytes, Regulatory, Epigenesis, Genetic, Mice, Genetic, Settore BIO/13 - Biologia Applicata, medicine, Transcriptional regulation, Animals, Epigenetics, Gene, Inbred BALB C, Genetics, Regulation of gene expression, Mice, Inbred BALB C, Multidisciplinary, Binding Sites, FOXP3, hemic and immune systems, Forkhead Transcription Factors, DNA Methylation, Biological Sciences, Regulatory, Cap analysis gene expression, Mice, Inbred C57BL, medicine.anatomical_structure, Gene Expression Regulation, DNA methylation, Transcription, Epigenesis
Abstract

Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that Treg-specific DNA hypomethylated regions were closely associated with Treg up-regulated transcriptional start site clusters, whereas Foxp3 binding regions had no significant correlation with either up- or down-regulated clusters in nonactivated Treg cells. However, in activated Treg cells, Foxp3 binding regions showed a strong correlation with down-regulated clusters. In accordance with these findings, the above two features of activation-dependent gene regulation in Treg cells tend to occur at different locations in the genome. The results collectively indicate that Treg-specific DNA hypomethylation is instrumental in gene up-regulation in steady state Treg cells, whereas Foxp3 down-regulates the expression of its target genes in activated Treg cells. Thus, the two events seem to play distinct but complementary roles in Treg-specific gene expression.

Published
2014

35. KeyGenes, a Tool to Probe Tissue Differentiation Using a Human Fetal Transcriptional Atlas

Author

Roost, M.S., Iperen, L. van, Ariyurek, Y., Buermans, H.P., Arindrarto, W., Devalla, H.D., Passier, R., Mummery, C.L., Carlotti, F., Koning, E.J. de, Zwet, E.W. van, Goeman, J.J., Chuva de Sousa Lopes, S.M., Roost, M.S., Iperen, L. van, Ariyurek, Y., Buermans, H.P., Arindrarto, W., Devalla, H.D., Passier, R., Mummery, C.L., Carlotti, F., Koning, E.J. de, Zwet, E.W. van, Goeman, J.J., and Chuva de Sousa Lopes, S.M.

Abstract

Contains fulltext : 153247.pdf (publisher's version ) (Open Access), Differentiated derivatives of human pluripotent stem cells in culture are generally phenotypically immature compared to their adult counterparts. Their identity is often difficult to determine with certainty because little is known about their human fetal equivalents in vivo. Cellular identity and signaling pathways directing differentiation are usually determined by extrapolating information from either human adult tissue or model organisms, assuming conservation with humans. To resolve this, we generated a collection of human fetal transcriptional profiles at different developmental stages. Moreover, we developed an algorithm, KeyGenes, which uses this dataset to quantify the extent to which next-generation sequencing or microarray data resemble specific cell or tissue types in the human fetus. Using KeyGenes combined with the human fetal atlas, we identified multiple cell and tissue samples unambiguously on a limited set of features. We thus provide a flexible and expandable platform to monitor and evaluate the efficiency of differentiation in vitro.

Published
2015

36. Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function

Author

Birket, M.J. (Matthew J.), Ribeiro, M.C. (Marcelo C.), Kosmidis, G. (Georgios), Ward, D. (Dorien), Leitoguinho, A.R. (Ana Rita), van de Pol, V. (Vera), Dambrot, C. (Cheryl), Devalla, H.D. (Harsha D.), Davis, R.P. (Richard P.), Mastroberardino, P.G. (Pier), Atsma, D.E. (Douwe), Passier, R. (Robert), Mummery, C.L. (Christine), Birket, M.J. (Matthew J.), Ribeiro, M.C. (Marcelo C.), Kosmidis, G. (Georgios), Ward, D. (Dorien), Leitoguinho, A.R. (Ana Rita), van de Pol, V. (Vera), Dambrot, C. (Cheryl), Devalla, H.D. (Harsha D.), Davis, R.P. (Richard P.), Mastroberardino, P.G. (Pier), Atsma, D.E. (Douwe), Passier, R. (Robert), and Mummery, C.L. (Christine)

Abstract

Maximizing baseline function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is essential for their effective application in models of cardiac toxicity and disease. Here, we aimed to identify factors that would promote an adequate level of function to permit robust single-cell contractility measurements in a human induced pluripotent stem cell (hiPSC) model of hypertrophic cardiomyopathy (HCM). A simple screen revealed the collaborative effects of thyroid hormone, IGF-1 and the glucocorticoid analog dexamethasone on the electrophysiology, bioenergetics, and contractile force generation of hPSC-CMs. In this optimized condition, hiPSC-CMs with mutations in MYBPC3, a gene encoding myosin-binding protein C, which, when mutated, causes HCM, showed significantly lower contractile force generation than controls. This was recapitulated by direct knockdown of MYBPC3 in control hPSC-CMs, supporting a mechanism of haploinsufficiency. Modeling this disease in vitro using human cells is an important step toward identifying therapeutic interventions for HCM.

Published
2015
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37. Atrial-like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial-selective pharmacology

Author

Devalla, HD, Schwach, V, Ford, JW, Milnes, JT, El-Haou, S, Jackson, C, Gkatzis, K, Elliott, DA, Lopes, SMCDS, Mummery, CL, Verkerk, AO, Passier, R, Devalla, HD, Schwach, V, Ford, JW, Milnes, JT, El-Haou, S, Jackson, C, Gkatzis, K, Elliott, DA, Lopes, SMCDS, Mummery, CL, Verkerk, AO, and Passier, R

Abstract

Drugs targeting atrial-specific ion channels, Kv1.5 or Kir3.1/3.4, are being developed as new therapeutic strategies for atrial fibrillation. However, current preclinical studies carried out in non-cardiac cell lines or animal models may not accurately represent the physiology of a human cardiomyocyte (CM). In the current study, we tested whether human embryonic stem cell (hESC)-derived atrial CMs could predict atrial selectivity of pharmacological compounds. By modulating retinoic acid signaling during hESC differentiation, we generated atrial-like (hESC-atrial) and ventricular-like (hESC-ventricular) CMs. We found the expression of atrial-specific ion channel genes, KCNA5 (encoding Kv1.5) and KCNJ3 (encoding Kir 3.1), in hESC-atrial CMs and further demonstrated that these ion channel genes are regulated by COUP-TF transcription factors. Moreover, in response to multiple ion channel blocker, vernakalant, and Kv1.5 blocker, XEN-D0101, hESC-atrial but not hESC-ventricular CMs showed action potential (AP) prolongation due to a reduction in early repolarization. In hESC-atrial CMs, XEN-R0703, a novel Kir3.1/3.4 blocker restored the AP shortening caused by CCh. Neither CCh nor XEN-R0703 had an effect on hESC-ventricular CMs. In summary, we demonstrate that hESC-atrial CMs are a robust model for pre-clinical testing to assess atrial selectivity of novel antiarrhythmic drugs.

Published
2015

38. Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function

Author

Birket, MJ, Ribeiro, MC, Kosmidis, G, Ward, D, Leitoguinho, AR, van de Pol, V, Dambrot, C, Devalla, HD, Davis, RP, Mastroberardino, Pier, Atsma, DE, Passier, R, Mummery, CL, Birket, MJ, Ribeiro, MC, Kosmidis, G, Ward, D, Leitoguinho, AR, van de Pol, V, Dambrot, C, Devalla, HD, Davis, RP, Mastroberardino, Pier, Atsma, DE, Passier, R, and Mummery, CL

Abstract

Maximizing baseline function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is essential for their effective application in models of cardiac toxicity and disease. Here, we aimed to identify factors that would promote an adequate level of function to permit robust single-cell contractility measurements in a human induced pluripotent stem cell (hiPSC) model of hypertrophic cardiomyopathy (HCM). A simple screen revealed the collaborative effects of thyroid hormone, IGF-1 and the glucocorticoid analog dexamethasone on the electrophysiology, bioenergetics, and contractile force generation of hPSC-CMs. In this optimized condition, hiPSC-CMs with mutations in MYBPC3, a gene encoding myosin-binding protein C, which, when mutated, causes HCM, showed significantly lower contractile force generation than controls. This was recapitulated by direct knockdown of MYBPC3 in control hPSC-CMs, supporting a mechanism of haploinsufficiency. Modeling this disease in vitro using human cells is an important step toward identifying therapeutic interventions for HCM.

Published
2015

43. Inhibition of ROCK improves survival of human embryonic stem cell-derived cardiomyocytes after dissociation

Author

Braam, S.R., Nauw, R., Ward-van Oostwaard, D., Mummery, C., Passier, R., Beyar, R., and Landesberg, A.

Abstract

In recent years the differentiation efficiency of human embryonic stem cells (hESCs) to cardiomyocytes has improved considerably. In general, hESC-derived cardiomyocytes are formed in aggregates, which require dissociation for follow-up experimental analyses and (clinical) applications. Here, we show that inhibition of the Rho-associated kinase (ROCK) by Y-27632 improved survival of dissociated hESC-derived differentiated cells. A maximum effect on cell survival was already observed within the first 24 hours. Hereafter, no further differences in the percentage of apoptotic and proliferating cells were observed with or without ROCK-inhibitor treatment. Improved survival was observed in both cardiomyocyte as well as non-cardiomyocyte cell populations. Viable cardiomyocytes were indicated by the appearance of beating, sarcomeric organization of cardiac-specific proteins, and fluorescence of a mitochondrion-selective dye. These results facilitate development of applications of hESC-derived cardiomyocytes in multiple research areas. Furthermore, these findings may be applied to other cell types differentiated from hESCs or other stem cells.

Published
2010

45. Three dimensional time dependent model with two photoactive centres for photorefractive spatial solitons in LiNbO3

Author

Devaux, F., Chauvet, M., Safioui, J., Passier, R., Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Condensed Matter::Strongly Correlated Electrons
Abstract

We present a new 3D time dependent model for photorefractive beam self focusing in undoped biased LiNbO 3 where iron impurities and Nb Li polarons are considered as two photoactive centres. Focusing or defocusing regimes are exhibited with respect to beam intensity and bias voltage in good agreement with experiments.

Published
2009

46. Soliton-induced waveguides in photorefractive LiNbO3 crystal

Author

Passier, R., Safioui, J., Chauvet, M., Devaux, F., Coda, V., Pettazzi, F., Alonzo, M., Fazio, E., Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Matériaux Optiques, Photonique et Systèmes (LMOPS), CentraleSupélec-Université de Lorraine (UL), Ultrafast Photonics Laboratory, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], European Space Research and Technology Centre (ESTEC), and European Space Agency (ESA)

Subjects
[PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic
Published
2009

47. Propagation de vortex optiques en milieu photoréfractif: application à la génération de guides optiques

Author

Passier, R., Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté, and Fabrice Devaux et Mathieu Chauvet

Subjects
[SPI]Engineering Sciences [physics], photorefractive optics, vortex, Optique non-linéaire, photovoltaïque, Non-linear optics, solitons, self-focusing, milieu photoréfractif, electro-optical materials, guides d'ondes, effet électro-optique, photovoltaic materials
Abstract

This work deals with the generation and handling of optical vortices, ie laser beams holders of a phase singularity providing an orbital angular momentum. The aim is to induce optical waveguides in photorefractive materials such as lithium niobate while also understanding the physical interactions between vortices and the non linear environment. The layout and manipulation of optical vortices are used here to achieve waveguides in massive materials. New technologies-wise, they could process information through new interconnections components. Our solution is based on the principle of spatial optical solitons, invariably propagating beams which can be obtained via an appropriate nonlinear interaction. Photorefractive spatial solitons are associated with a refractive index modulation by the Pockels effect that induces a waveguide in an optical material with the same profile as the soliton's. We propose here to use an efficient material in the field of optoelectronics, the lithium niobate (LiNbO3).We first introduce the basics and the state of the art on solitons and on optical vortices and their applications are also featured. Then the principles involved in this work are detailed. On one hand, the mathematical formalism defining vortices and methods for obtaining them are described. On the other hand, the different physical mechanisms participating to the formation of solitons in photorefractive materials are described. We then expose the well-known numerical models describing the phenomenons, detailing their strengths and imperfections. A new three dimensional and time numerical model incorporating variables previously neglected is proposed for a better understanding of the behavior of vortices in lithium niobate doped iron. In Chapter Four, we highlight the good agreement between this new model and the experimental observation of the influence of crystal anisotropy on the propagation of a vortex in a photorefractive-photovoltaic according to parameters such as the orbital momentum of the vortex and the directions of propagation and polarization with respect to crystallographic axes of LiNbO3. In the last chapter, the results obtained in the previous one are used to define the optimal experimental conditions to form a quasi-vortex soliton in two dimensions, inducing a structure confining light in the material. In addition, the first experimental complex structures optically induced by vortices with multiple charges are presented.The new numerical model developed in this thesis may be used to go into details of dislocation mechanisms and dynamics of optical vortex related to the presence of multiple phase singularities.; Ce manuscrit porte sur la génération, la mise en forme et la manipulation de vortex optiques, c'est à dire de faisceaux laser porteurs de singularités de phase les dotant d'un moment orbital angulaire. Nous les utilisons pour photoinduire des guides optiques dans des matériaux photoréfractifs tels que le niobate de lithium tout en s'attachant à la compréhension physique des interactions vortex/milieu photoréfractif. La mise en forme et la manipulation de vortex optiques s'inscrit ici dans la perspective de réalisation de systèmes guidants dans des matériaux massifs. Liés aux nouvelles technologies, ils pourraient permettre de traiter l'information via de nouveaux composants d'interconnections. Notre solution est basée sur le principe des solitons optiques spatiaux, faisceaux invariants en propagation qui peuvent être obtenus via une interaction non linéaire appropriée. Les solitons spatiaux photoréfractifs sont associés à une modification de l'indice de réfraction du matériau par effet Pockels qui induit un guide optique au sein du matériau ayant le même profil que le soliton. Nous utilisons ici un matériau qui a fait ses preuves dans le domaine de l'optoélectronique, le niobate de lithium (LiNbO3).Nous présentons d'abord les notions de base relatives aux solitons et les différents moyens permettant de les obtenir. Les vortex optiques et leurs applications sont également introduits. Plus précisément, le formalisme mathématique définissant les vortex et les méthodes pour les obtenir sont décrits. D'autre part, les différents mécanismes physiques intervenant dans la formation de solitons spatiaux dans les matériaux photoréfractifs sont détaillés. Un nouveau modèle numérique intégrant des variables auparavant négligées est proposé pour une meilleure compréhension du comportement du vortex dans le niobate de lithium dopé fer que les modèles numériques utilisés jusqu'alors. Nous mettons ensuite en évidence le bon accord entre ce nouveau modèle numérique et l'observation expérimentale de l'influence de l'anisotropie du cristal sur la propagation d'un vortex en milieu photoréfractif-photovoltaïque en fonction de paramètres tels que le moment orbital du vortex et les directions de propagation et de polarisation par rapport aux axes cristallographiques du LiNbO3. Enfin, les résultats obtenus dans le chapitre précédent sont mis à profit pour définir les conditions expérimentales optimales permettant d'obtenir un quasi-soliton noir en deux dimensions induisant une structure capable de guider et confiner la lumière dans le matériau. De plus les premiers résultats expérimentaux de structures guidantes plus complexes induites optiquement avec des vortex de charges multiples sont présentés.Le nouveau modèle numérique développé dans le cadre de cette thèse peut-être utilisé afin d'étudier de façon plus approfondie la dynamique des mécanismes de dislocation de vortex optiques lié à la présence de singularités de phases multiples.

Published
2009

49. Dynamical behaviour of vortices in refractive medium

Author

Passier, R., Devaux, F., Chauvet, M., Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2007

50. Structures guidantes 3-D induites par vortex optiques dans le LiNbO3

Author

Passier, R., Chauvet, M., Devaux, F., Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2006

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